DNA methylation is a biological process where methyl groups are added to DNA, changing gene expression without altering the DNA sequence. It is essential for normal development in mammals and is associated with processes like genomic imprinting and carcinogenesis. DNA methyltransferases are enzymes that catalyze the addition of methyl groups to DNA from S-adenosyl methionine. DNA methylation plays important roles in gene silencing, X-chromosome inactivation, and suppressing viral genomes and repetitive elements incorporated into the host genome. Abnormal DNA methylation is also associated with cancer by transcriptionally silencing tumor suppressor genes.
Dna methylation ppt
definition of Dna methylation ppt
discovery of Dna methylation ppt
types of Dna methylation ppt
history of Dna methylation ppt
process of Dna methylation ppt
mechanism of Dna methylation ppt
methylation in cancer
cytosine methylation
genomic imprinting
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supercoiling is one of the important process to condenses the huge amount of DNA to fit inside the histone and its also plays a role during the replication ,transcription etc..,these activities is carried out by an enzyme called topoisomerases.
Dna methylation ppt
definition of Dna methylation ppt
discovery of Dna methylation ppt
types of Dna methylation ppt
history of Dna methylation ppt
process of Dna methylation ppt
mechanism of Dna methylation ppt
methylation in cancer
cytosine methylation
genomic imprinting
Dna supercoiling and role of topoisomerasesYashwanth B S
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Chromatin is the complex combination of DNA and proteins that makes up chromosomes. It can be made visible by staining with specific techniques and stain (thus the name chromatin which literally means colored material). The major proteins involved in chromatin are histone proteins; although many other chromosomal proteins have prominent roles too. The functions of chromatin is to package DNA into smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and to serve as a mechanism to control gene expression and DNA replication.
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Epigenetics definition, history of epigenetics, molecular basis of epigenetics, epigenetic modification, tools to study epigenetics, disease linked with epigenetics, DNA methylation demethylation and enzymes regulating DNA methylation
4) Describe the role of methylation in regulating gene expression. (.pdfshanhairstonkirui643
4) Describe the role of methylation in regulating gene expression. (In other words, does it
promote or inhibit gene expression, what is methylated, and what proteins add or remove the
methylation groups (as applicable)?).
5) Describe the role of acetylation in control of gene expression. (In other words, does it promote
or inhibit gene expression, what is acetylated, and what enzymes add or remove the acetylation
groups?).
6) How does the charge of the histones within a nucleosome affect a cell’s transcriptional
activity? In other words, does making a histone octomer more or less positively charged have an
effect?
Solution
Answer:
4. DNA methylation is an epigenetic mechanism and involves the modifcation of DNA that
occurs through the addition of a methyl group to DNA strand itself. DNA methylation occurs at
the cytosine bases of eukaryotic DNA, which are converted to 5-methylcytosine by DNA
methyltransferase (DNMT) enzymes.
DNA methylation plays a crucial role in repressing gene expression, perhaps by blocking the
promoters at which activating transcription factors should bind. It appears that proper DNA
methylation is essential for cell differentiation and embryonic development.
In some cases, methylation has observed to play a role in mediating gene expression. Evidence
of this has been found in studies that show that methylation near gene promoters varies
considerably depending on cell type, with more methylation of promoters correlating with low or
no transcription. While overall methylation levels and completeness of methylation of particular
promoters are similar in individual humans, there are significant differences in overall and
specific methylation levels between different tissue types and between normal cells and cancer
cells from the same tissue.
The demethylation process is necessary for epigenetic reprogramming of genes and is also
directly involved in many important disease mechanisms such as tumor progression.
Demethylation of DNA can either be passive or active, or a combination of both.
Passive DNA demethylation usually takes place on newly synthesized DNA strands via DNMT1
during replication rounds. Active DNA demethylation mainly occurs by the removal of 5-
methylcytosine via the sequential modification of cytosine bases..
The epigenetic regulation of DNA-templated processes has been intensely studied over the last 15
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present the basic principles behind these epigenetic pathways and highlight the evidence suggesting that their misregulation can culminate in cancer. This information, along with the promising clinical and preclinical results seen with epigenetic drugs against chromatin regulators, signifies that it
is time to embrace the central role of epigenetics in cancer.
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2. INTRODUCTION
DNA methylation is a biological process by which methyl
groups are added to the DNA molecule.
Methylation can change the activity of a DNA segment without
changing the sequence. When located in a gene promoter, DNA
methylation typically acts to repress gene transcription.
In mammals, DNA methylation is essential for normal
development and is associated with a number of key processes
including genomic imprinting, X-chromosome inactivation,
aging, and carcinogenesis.
3. DNA Methylation of most organism is modified by a post
replicative process which resuls in three types of
methylated bases in DNA:
C5-methylcytosine
N4-methylcytosine
N6-methylcytosine
This modification is called DNA Methylation.
DNA Methylation is a covalent modification of DNA that
does not change the DNA sequence, but had an influence
on gene activity.
4. It occurs in the cells of fungi, plants, non-vertebrates
and vertebrates.
In vertebrates , 3-6% of DNA cytosine is methylated.
No methylation in many insects and single celled
eukaryotes.
In plants, 30% of DNA cytosine is methylated.
5. Epigenetic Factor
DNA methylation is an epigenetic mechanism that occurs by the
addition of a methyl (CH3) group to DNA, thereby often modifying the
function of the genes and affecting gene expression.
The most widely characterized DNA methylation process is the
covalent addition of the methyl group at the 5-carbon of the cytosine
ring resulting in 5-methylcytosine (5-mC), also informally known as the
“fifth base” of DNA.
These methyl groups project into the major groove of DNA and inhibit
transcription.
6. Mechanism
Methyl groups are transferred from S-adenosyl
methionine in a rection catalysed by a DNA methyl
transferases.
SAM is then converted SAH i.e S-Adenosyl
homocysteine.
7. Enzymes Involved In DNA
Methylation
The addition of methyl groups is controlled at several different levels in
cells and is carried out by a family of enzymes called DNA
methyltransferases (DNMTs).
DNMTs catalyses the reaction at different times during the cell cycle.
In mammals:
1. DNMT1-Maintanence methylase
2. DNMT 2
3. DNMT 3a and DNMT 3b
4. DNMT 3L
8. Enzymes
DNMT 1:
• Maintains the pattern of DNA methylation after DNA replication.
• Requires a hemi-methylated DNA substrate and will faithfully reproduce the pattern of DNA
methylation on the newly synthesized strands.
• DNA methylation- “an automatic semi conservative mechanism”
DNAMT 3a and DNMT 3B:
• This will add methyl groups to C G dinucleotides which are previously unmethylated on both the
strands.
• It re-establish the methylation pattern.
9.
10. Active Methylation:
Active DNA demethylation is mediated by multiple
enzymes and can occur independent of DNA replication.
Passive Methylation:
The passive process takes place in the absence of methylation
of newly synthesised DNA strands by DNMT1 during several
replication rounds, leading to dilution of the methylation
signal.
11.
12. Role of DNA Methylation
It plays a role in long term silencing of gene.
It plays a role in silencing of repetititve elements.
It plays a role in X-chromosome inactivation.
In the establishment and maintenance of imprinted genes.
Supress the expression of viral genome and other
deletrorious element that have an incorporated into the
genome of the host over time.
13. DNA methylation in Stem Cells
DNA methylation mechanism has been characterized in
embryonic stem cells. Although this in vitro model may predict
the function of DNA methylation in a dividing cell.
Embryonic stem cells are an inadequate model for studying DNA
methylation in a postmitotic cell.
The fact that DNMTs are required for normal neuronal
differentiation and maturation hinders the study of DNA
methylation solely in postmitotic neurons.
Despite these limitations, two models have emerged to study
DNA methylation in postmitotic neurons.
14. DNA Methylation in Cancer
• DNA methylation in cancer plays a variety of roles, helping to change the
healthy regulation of gene expression to a disease pattern.
• All mammalian cells descended from a fertilized egg share a common DNA sequence.
However, during development and formation of different tissues epigenetic factors change.
• The changes include histone modifications, CpG island methylations and chromatin
reorganizations which can cause the stable silencing or activation of particular genes.
• Once differentiated tissues are formed, CpG island methylation is generally stably inherited
from one cell division to the next through the DNA methylation maintenance machinery.
15. • In cancer, a number of mutational changes are found in protein coding
genes. Colorectal cancers typically have 3 to 6 driver mutations and 33 to
66 hitchhiker or passenger mutations that silence protein expression in the
genes affected.
• However, transcriptional silencing may be more important than mutation
in causing gene silencing in progression to cancer.
• In colorectal cancers about 600 to 800 genes are transcriptionally
silenced, compared to adjacent normal-appearing tissues, by CpG island
methylation. Transcriptional repression in cancer can also occur by
other epigenetic mechanisms, such as altered expression of micro-RNAs.
16. Conclusion
DNA methylation represents an annotation system for marking the genetic text, thus providing
instruction as to how and when to read the information and control transcription.
Unlike sequence information, which is inherited, methylation patterns are established in a
programmed process that continues throughout development, thus setting up stable gene expression
profiles.
This DNA methylation paradigm is a key player in medicine. Some changes in methylation closely
correlate with age providing a marker for biological ageing, and these same sites could also play a
part in cancer.
The genome continues to undergo programmed variation in methylation after birth in response to
environmental inputs, serving as a memory device that could affect ageing and predisposition to
various metabolic, autoimmune, and neurological diseases.
Taking advantage of tissue-specific differences, methylation can be used to detect cell death and
thereby monitor many common diseases with a simple cell-free circulating-DNA blood test.